Animal models which have been developed for the study of pancreatic cancer are characterized by species specificity. The inability of target tissue to adequately repair DNA damage is one factor which has been related to carcinogenicity in other systems. Inducible, adaptive responses to DNA damage, in particular, have been shown to be important in regard to mutagenesis and carcinogenesis. Thus, the overall objectives of this proposal are: 1) To study constitutive and inducible, presumably error-free, DNA repair functions in the pancreas of two species, rat and hamster, and compare levels of these functions with those in the liver of these two species. Levels of O6-methylguanine removal activity as well as levels of 3-methyladenine-DNA glycosylase, 7-methylguanine-DNA glycosylase and uracil-DNA glycosylase will be determined. Inducibility of these activities will be studies in response to stimulation of DNA synthesis and carcinogen pretreatment; and 2) To determine whether there are inducible post-replication SOS-type DNA repair functions in the pancreas of rat and hamster by studying enhanced reactivation and mutagenesis of Herpes simplex virus I and the effects of carcinogen treatment on initiation and elongation during DNA replication.